Unmasking a temperature-dependent effect of the<i>P. anserina</i>i-AAA protease on aging and development

Weil, Andrea; Luce, K. Scott; Dröse, Stefan; Wittig, Ilka; Brandt, Ulrich; Osiewacz, Heinz D.

doi:10.4161/cc.10.24.18560

Cited by 32 publications

(39 citation statements)

References 57 publications

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“…Such a function can explain the counterintuitive results of specific, well-defined experiments that otherwise lead to false conclusions. We have previously obtained similar counterintuitive results when we ablated the mitochondrial AAA protease PaIAP, a protein of the inner mitochondrial membrane of P. anserina that is involved in mitochondrial 48 . Under standard laboratory growth conditions at 27°C the life span of the mutant is strongly increased.…”

Section: Discussionmentioning

confidence: 57%

Stress-dependent opposing roles for mitophagy in aging of the ascomycete Podospora anserina

et al. 2017

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Mitochondrial dysfunction is causatively linked to organismal aging and the development of degenerative diseases. Here we describe stress-dependent opposing roles of mitophagy, the selective autophagic degradation of mitochondria, in aging and life-span control. We report that the ablation of the mitochondrial superoxide dismutase which is involved in reactive oxygen species (ROS) balancing, does not affect life span of the fungal aging model Podospora anserina, although superoxide levels are strongly increased and complex I-dependent respiration is impaired. This unexpected phenotype depends on functional autophagy, particularly mitophagy, which is upregulated during aging of this mutant. It identifies mitophagy as a prosurvival response involved in the control of mitohormesis, the well-known beneficial effect of mild mitochondrial oxidative stress. In contrast, excessive superoxide stress turns mitophagy to a prodeath pathway and leads to accelerated aging. Overall our data uncover mitophagy as a dynamic pathway that specifically responds to different levels of mitochondrial oxidative stress and thereby affects organismal aging.

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Section: Discussionmentioning

confidence: 57%

Stress-dependent opposing roles for mitophagy in aging of the ascomycete Podospora anserina

et al. 2017

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“…Female fertility was assessed as previously described 25 . In principle, freshly isolated monokaryotic wild-type or Paatg1 Δ isolates of both mating types were allowed to overgrow the surface of M2 agar (M2 medium: 0.25 g/L KH 2 PO 4 , 0.3 g/L K 2 HPO 4 , 0.25 g/L MgSO 4 × 7 H 2 O, 0.5 g/L urea and 10 g/L yellow dextrin.…”

Section: Methodsmentioning

confidence: 99%

“…In particular, it has been found that overexpression of PaLon encoding a mitochondrial matrix protease leads to an increased healthy life span 22 while the deletion of the gene shortens life span 23 . PaCLPP, another mitochondrial matrix protease, and PaIAP, the iAAA protease of the inner mitochondrial membrane of P. anserina , are involved in temperature-dependent protein quality control 24 , 25 . Finally, the manipulation of reactions of the apoptotic cell death machinery, that brings the life of P. anserina to an end, has been found to strongly affect life span 26 - 28 …”

Section: Introductionmentioning

confidence: 99%

Identification of autophagy as a longevity-assurance mechanism in the aging modelPodospora anserina

Knuppertz

Hamann

Pampaloni³

et al. 2014

Autophagy

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The filamentous ascomycete Podospora anserina is a well-established aging model in which a variety of different pathways, including those involved in the control of respiration, ROS generation and scavenging, DNA maintenance, proteostasis, mitochondrial dynamics, and programmed cell death have previously been demonstrated to affect aging and life span. Here we address a potential role of autophagy. We provide data demonstrating high basal autophagy levels even in strains cultivated under noninduced conditions. By monitoring an N-terminal fusion of EGFP to the fungal LC3 homolog PaATG8 over the lifetime of the fungus on medium with and without nitrogen supplementation, respectively, we identified a significant increase of GFP puncta in older and in nitrogen-starved cultures suggesting an induction of autophagy during aging. This conclusion is supported by the demonstration of an age-related and autophagy-dependent degradation of a PaSOD1-GFP reporter protein. The deletion of Paatg1, which leads to the lack of the PaATG1 serine/threonine kinase active in early stages of autophagy induction, impairs ascospore germination and development and shortens life span. Under nitrogen-depleted conditions, life span of the wild type is increased almost 4-fold. In contrast, this effect is annihilated in the Paatg1 deletion strain, suggesting that the ability to induce autophagy is beneficial for this fungus. Collectively, our data identify autophagy as a longevity-assurance mechanism in P. anserina and as another surveillance pathway in the complex network of pathways affecting aging and development. These findings provide perspectives for the elucidation of the mechanisms involved in the regulation of individual pathways and their interactions.

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“…Recent work demonstrated a clear impact of mitochondrial protein quality control on the regulation of lifespan and stress adaptation in this model organism101217.…”

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confidence: 98%

Human CLPP reverts the longevity phenotype of a fungal ClpP deletion strain

et al. 2013

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Mitochondrial maintenance crucially depends on the quality control of proteins by various chaperones, proteases and repair enzymes. While most of the involved components have been studied in some detail, little is known on the biological role of the CLPXP protease complex located in the mitochondrial matrix. Here we show that deletion of PaClpP, encoding the CLP protease proteolytic subunit CLPP, leads to an unexpected healthy phenotype and increased lifespan of the fungal ageing model organism Podospora anserina. This phenotype can be reverted by expression of human ClpP in the fungal deletion background, demonstrating functional conservation of human and fungal CLPP. Our results show that the biological role of eukaryotic CLP proteases can be studied in an experimentally accessible model organism.

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Unmasking a temperature-dependent effect of theP. anserinai-AAA protease on aging and development

Cited by 32 publications

References 57 publications

Stress-dependent opposing roles for mitophagy in aging of the ascomycete Podospora anserina

Stress-dependent opposing roles for mitophagy in aging of the ascomycete Podospora anserina

Identification of autophagy as a longevity-assurance mechanism in the aging modelPodospora anserina

Human CLPP reverts the longevity phenotype of a fungal ClpP deletion strain

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